Δ9-Tetrahydrocannabinol and Endogenous Cannabinoid Anandamide Directly Potentiate the Function of Glycine Receptors

@article{Hejazi20069TetrahydrocannabinolAE,
  title={$\Delta$9-Tetrahydrocannabinol and Endogenous Cannabinoid Anandamide Directly Potentiate the Function of Glycine Receptors},
  author={Nadia S Hejazi and Chunyi Zhou and Murat Oz and Hui Sun and Jiang Hong Ye and Li Zhang},
  journal={Molecular Pharmacology},
  year={2006},
  volume={69},
  pages={991 - 997}
}
Anandamide (AEA) and Δ9-tetrahydrocannabinol (THC) are endogenous and exogenous ligands, respectively, for cannabinoid receptors. Whereas most of the pharmacological actions of cannabinoids are mediated by CB1 receptors, there is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Here, we report that THC and AEA, in a CB1 receptor-independent manner, cause a significant potentiation of the amplitudes of glycine… 
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References

SHOWING 1-10 OF 57 REFERENCES
The Endogenous Cannabinoid Anandamide Inhibits α7 Nicotinic Acetylcholine Receptor-Mediated Responses in Xenopus Oocytes
TLDR
It is demonstrated that the endogenous cannabinoid anandamide inhibits the function of nACh α7 receptors expressed in Xenopus oocytes in a cannabinoid receptor-independent and noncompetitive manner.
Levels, Metabolism, and Pharmacological Activity of Anandamide in CB1 Cannabinoid Receptor Knockout Mice
Abstract: Anandamide [arachidonylethanolamide (AEA)] appears to be an endogenous agonist of brain cannabinoid receptors (CB1), yet some of the neurobehavioral effects of this compound in mice are
Anandamide, an Endogenous Cannabinoid, Inhibits Shaker-related Voltage-gated K+ Channels
TLDR
It is reported that anandamide directly inhibits (IC50, 2.7 muM) Shaker-related Kv1.2 K+ channels that are found ubiquitously in the mammalian brain.
Glycine Receptors in CNS Neurons as a Target for Nonretrograde Action of Cannabinoids
TLDR
It is demonstrated that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels and that the direct inhibition of GlyRs by endocannabinoids can modulate the hippocampal network activity.
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.
Additive Effects of Endogenous Cannabinoid Anandamide and Ethanol on α7-Nicotinic Acetylcholine Receptor-Mediated Responses in Xenopus Oocytes
TLDR
Analysis of Xenopus oocytes by matrix-assisted laser desorption/ionization technique indicated that ethanol treatment did not alter the lipid profile of oocytes, and there is negligible, if any, anandamide present in these cells.
Receptor-independent effects of endocannabinoids on ion channels.
  • M. Oz
  • Chemistry, Medicine
    Current pharmaceutical design
  • 2006
TLDR
Results indicate that additional molecular targets for endocannabinoids exist and that these targets may represent important sites for cannabinoids to alter either the excitability of the neurons or the response of the neuronal systems.
Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons.
  • P. Fan
  • Chemistry, Medicine
    Journal of neurophysiology
  • 1995
TLDR
The action of cannabinoid agonists on 5-HT3 receptors may be a possible mechanism for some of the behavioral effects of cannabinoids, such as antiemesis and analgesia, when investigated in rat nodose ganglion neurons.
Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5‐HT3 receptor‐mediated responses in Xenopus oocytes
TLDR
It is demonstrated that the endogenous cannabinioid anandamide inhibits the function of 5‐HT3 receptors expressed in Xenopus oocytes in a cannabinoid‐receptor independent and noncompetitive manner.
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice.
TLDR
Most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor, which accounts for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications.
...
1
2
3
4
5
...